Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta 2 glycoprotein I (apolipoprotein H, beta 2GPI) is involved in the formation of epitope(s) recognized by clinically relevant autoantibodies from patients with antiphospholipid syndrome. We studied the binding of beta 2GPI to chemically activated polystyrene in a microtitre plate format. Adsorption isotherms (at 37 degrees C) were generated for beta 2GPI on activated polystyrene and on unactivated polystyrene, with both human serum antibodies and rabbit polyclonal IgG antibodies as probes, and horseradish peroxidase (HRP)-tagged anti-IgG to detect binding. Additionally, beta 2GPI was biotinylated and isotherms were developed by using HRP-streptavidin as the recognition sequence. Human serum autoantibodies, which did not precipitate beta 2GPI in solution, yielded a characteristic chemisorption isotherm on activated polystyrene but did not recognize beta 2GPI bound to untreated polystyrene. The rabbit IgG, which did precipitate beta 2GPI in solution, detected beta 2GPI bound to both activated polystyrene and, to a lesser extent, to untreated polystyrene. The binding of beta 2GPI to untreated polystyrene was confirmed by the use of biotinylated beta 2GPI. To assess the prevalence of IgG anti-beta 2GPI autoantibodies, we surveyed 113 sera submitted to our laboratory for anticardiolipin antibody (aCL) testing. Only nine (8%) had anti-beta 2GPI activity greater than two standard deviations above the mean for those sera in which aCL activity was within normal limits. We conclude that epitope presentation of beta 2GPI for human autoantibody binding is dependent on surface properties of the polystyrene, and that beta 2GPI autoantibodies are found only in a subpopulation of sera positive for aCL.
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PMID:Binding of beta 2 glycoprotein I to activated polystyrene and its recognition by human IgG autoantibodies. 857 91

Autoimmune antiphospholipid antibodies are a hallmark of patients with antiphospholipid syndrome, and require a protein cofactor, beta 2-glycoprotein I, to bind anionic phospholipids. In these same patients, moreover, IgG directly binding beta 2-glycoprotein I are described. We found high plasma titres of both IgM and IgG anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. After passing plasma through a Sephacryl S-300 column, an identical distribution pattern between anti beta 2- glycoprotein I and anticardiolipin antibodies was observed. Moreover, when IgG immunocomplexes were isolated from a high molecular fraction, IgM anti- beta 2-glycoprotein I and anticardiolipin antibodies were detected. Thus IgG, IgM ad IgG-IgM complexes of anti-beta 2-glycoprotein I antibodies are present at the same time in a patient with antiphospholipid syndrome.
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PMID:Anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. 860 82

The pathogenesis of the antiphospholipid syndrome remains uncertain. Antibodies that react with phospholipids may not be directly responsible for cellular injury, but may be part of the immune network through which autoantibodies with pathogenic potential are generated. The latter may recognize proteins such as beta 2-glycoprotein I that form complexes with phospholipids, proteins whose functions depend upon interaction with phospholipids such as protein C and its cofactors, altered lipoproteins such as oxidized low-density lipoproteins, or other molecules that share only antigenic similarity. Thus, a spectrum of autoantibodies that recognize different lipid-protein complexes may develop in these patients and contribute to the observed clinical heterogeneity of the syndrome. Current techniques do not permit identification of the subset of patients with antiphospholipid antibodies at risk for thrombosis or abortion and there are no prospective, controlled trials addressing the prophylaxis or treatment of affected individuals. Identification of the cellular targets of antibodies to lipid-protein moieties is needed to identify patients at risk for these complications and as a means to monitor therapy.
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PMID:The antiphospholipid-protein syndrome. 861 97

The aim of this study was to analyse the prevalence and isotype distribution of antibodies to endothelial cells (aEC) and to beta 2-glycoprotein I (a beta 2GPI) in the antiphospholipid syndrome (APS). Fifteen patients with an APS [nine associated with systemic lupus erythematosus (SLE) and six "primary'] and 15 with SLE without an APS were prospectively studied. The aEC were determined by an enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein and the a beta 2GPI by ELISA using highly purified beta 2GPI. A positive titre of aEC was detected in 20 out of 30 patients (67%), but in none of the control group. Ten patients had both IgG and IgM isotypes, five had IgG only and five had only IgM. Thirteen patients with the APS (87%) were found to have a positive titre of aEC, while only seven with SLE but without a history of APS (47%) had aEC (P < 0.05). Nine patients with the APS (60%) had a positive titre of a beta 2GPI (four had both IgG and IgM isotypes, one had IgG only and four had only IgM), while none of the patients without an APS (0%) had these antibodies (P < 0.001). A significant association was also found between the presence of aPL and aEC (P < 0.05), as well as between aPL and a beta 2GPI (P < 0.001). Both aEC and a beta 2GPI can be found in the APS. This reinforces the theory that APS represents a complex autoimmune disorder in which several autoantibodies co-exist with aPL.
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PMID:Antibodies to endothelial cells and to beta 2-glycoprotein I in the antiphospholipid syndrome: prevalence and isotype distribution. 867 May 71

Since the recognition of the antiphospholipid syndrome, a great number of cardiac manifestations have been reported in association with these antibodies: valvular disease, coronary artery disease, cardiomyopathy and intracardiac thrombosis. However this association raises numerous questions related to the pathogenic role of antiphospholipids, their prognostic significance and their frequency in a non-selected population with a definite cardiac manifestation. In view of the literature and our personal experience, it seems necessary to distinguish two kinds of situations. During systemic lupus and primary antiphospholipid syndrome (which must be systematically looked for in patients with history of thrombo-embolic disease), antiphospholipids antibodies certainly play a role in the occurrence of cardiac manifestations, but the precise place of thrombosis has to be best defined along with immunologic/inflammatory mechanisms. On the other hand, in a non-selected population, antiphospholipids antibodies may just be the consequence of the cardiac lesion and do not seem to have prognostic implications. This distinction, actually hypothetical, should be supported on the basis of distinct specificities of antiphospholipids antibodies and especially their dependence on beta 2-glycoprotein I, which would help to distinguish the harmful antibodies from those which probably just appear as an epiphenomenon.
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PMID:[The heart and antiphospholipid antibodies. Personal experience and review of the literature]. 867 84

A portion of anticardiolipin antibodies is defined as phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies and recognizes the conformationally altered beta 2 GPI which interacts with anionic phospholipids. We studied the clinical significance of IgG phospholipid-dependent anti-beta 2-GPI antibodies in patients with antiphospholipid syndrome (APS). The subjects consisted of 60 APS patients. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected by ELISA in 32 of the 60 patients (53%). Significantly higher incidences of prolonged APTT and lupus anticoagulants were found in patients with these anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash, serositis, LE cell preparation and anti-Sm antibodies were found in patients with these anti-beta 2-GPI antibodies. It was found that 88% of the patients with these anti-beta 2-GPI antibodies satisfied less than five of the revised criteria items for the classification of SLE. These findings indicate the clinical characteristics of APS patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies.
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PMID:Phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies and antiphospholipid syndrome. 868 96

We measured serum antiphospholipid antibodies (aPL) in patients with multiple sclerosis (MS) using enzyme linked immunosorbent assay (ELISA) and examined the correlations between these antibodies and MS. This study included thirty-two patients with clinically definite MS, thirteen patients with other autoimmune neurological diseases excluding collagen diseases (disease control A), eight patients with collagen vascular diseases (disease control B) and twenty-six healthy persons (normal control). In MS group IgG antibody against cardiolipin (CL) was detected in 3 (9%); among them, cofactor (beta 2-glycoprotein I) dependency was shown in 2 but one was cofactor independent. IgM antibody was elevated in 14 of 32 patients (44%) with MS, but cofactor dependency was not determined. However, this was significantly higher in frequency than that of the disease control A (p < 0.01) and normal control (p < 0.01). Results of antibodies against phosphatidylserine were found similar to CL, but antibodies against phosphatidylcholine were in most cases negative. Each of anti-CL IgG antibody purified from four patients with diverse immunological disorders (primary antiphospholipid antibody syndrome, MS, polyarteritis nodosa and systemic lupus erythematosus) had different reactivities against DNA. In addition, the aPL positive group in MS possessed the autoantibodies such as antinuclear antibody at higher rate than the negative group. However, clinically two groups of MS were indistinguishable. The higher incidence of aPL may imply that a broad spectrum of autoantibodies might be produced in MS; some antibodies presumably related directly to MS pathogenesis are yet to be identified.
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PMID:Characterization of serum anti-phospholipid antibodies in patients with multiple sclerosis. 872 2

Antiphospholipid antibodies were originally thought to bind negatively-charged (anionic) phospholipids. Current evidence suggest that the target antigen is considerably more complex and includes beta 2-glycoprotein I, a phospholipid-binding plasma protein. Our understanding of the pathophysiology of the antiphospholipid syndrome has increased exponentially with a number of studies into the interactions of antiphospholipid antibodies and beta 2-glycoprotein I.
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PMID:The role of beta 2-glycoprotein I in the antiphospholipid syndrome. 874 29

We investigated the clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.
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PMID:Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus. 874 70

The Antiphospholipid Syndrome is defined by the association between peculiar clinical manifestations, namely arterial and/or venous thrombosis, recurrent abortions and thrombocytopenia, and the antiphospholipid antibodies. These antibodies are directed to plasma proteins bound to anionic phospholipids or other anionic surfaces: so far, beta 2-glycoprotein I is the best known and characterized antiphospholipid 'cofactor' (this issue is specifically treated in other parts of this journal). In recent years, such a role has been reported also for prothrombin, activated Protein C, Protein S, Annexin V, Thrombomodulin, high- and low-molecular weight kininogens. Anti-prothrombin antibodies are detected in approximately 50% of the antiphospholipid-positive patients; conversely, limited data are available regarding the prevalence the other antibodies. 'Cofactors' are necessary for the expression of both the immunological and the functional properties of their respective antiphospholipid antibodies. In particular, the recognition of the calcium-mediated prothrombin/lipid complex by anti-prothrombin antibodies hampers prothrombin activation, thus causing the prolongation of the phospholipid-dependent coagulation reactions. The interaction between antiphospholipid antibodies and natural inhibitors of coagulation such as activated Protein C, its non-enzymatic accessory protein Protein S or Thrombomodulin might increase the risk to develop thromboembolic events. Similarly, the presence of antibodies to surface-bound Annexin V has been hypothesized to play a role in recurrent abortions and fetal deaths. However, to clearly establish whether and which antiphospholipid antibodies represent risk factors for the thromboembolic events of the antiphospholipid syndrome, further studies of their behaviour and properties as well as the identification and characterization of (possibly) other antibodies are required.
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PMID:Non beta 2-glycoprotein I cofactors for antiphospholipid antibodies. 890 67


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